{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T11:55:43Z","timestamp":1787313343567,"version":"build-2736575974"},"reference-count":91,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:00:00Z","timestamp":1784246400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Committee of Science of the Ministry of Science and Higher Education of the Republic of Kazakhstan","award":["BR24992760"],"award-info":[{"award-number":["BR24992760"]}]},{"award":["BR24992760"],"award-info":[{"award-number":["BR24992760"]}],"id":[{"id":"https:\/\/ror.org\/05tyne317","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>This review examines recent quantum chemical methodologies applied to investigating antibiotic structure and mechanisms of action. The discussion is organised into three sections: (1) enzymatic hydrolysis of the \u03b2-lactam ring, (2) interactions of antibiotics with ribosomal subunits and enzyme active sites, and (3) complex formation with metal ions. Each section evaluates how quantum chemical approaches, particularly density functional theory (DFT) and hybrid QM\/MM techniques, model molecular processes relevant to antibiotic function, including transition states, electron density analyses, and metal coordination effects on antibacterial activity. Selected studies demonstrate the utility of these methodologies in interpreting experimental data and predicting physicochemical and biological properties of novel compounds. Distinct from previous literature, this review provides a comparative and up-to-date synthesis of quantum chemical methods related to enzymatic mechanisms and metal-based antibiotic systems, emphasising experimental validation strategies and practical guidelines for method selection in antibiotic research. It also identifies areas where quantum chemical modelling can integrate with experimental pharmacology and structural biology to support the rational design of next-generation antimicrobial agents. The review concludes by advocating an interdisciplinary framework combining quantum chemistry, biochemistry, and pharmacology to address antibiotic resistance. The review focuses primarily on antibiotics targeting bacterial cell wall and protein synthesis, particularly \u03b2-lactam antibiotics, ribosome-targeting agents, and their interactions with metal ions. Computational methods discussed are mainly limited to DFT, ab initio, and hybrid QM\/MM approaches. It does not cover membrane-disrupting antibiotics, antiviral or antifungal agents, machine learning-based prediction methods, or purely molecular dynamics approaches outside a quantum mechanical context.<\/jats:p>","DOI":"10.3390\/molecules31142493","type":"journal-article","created":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T09:00:52Z","timestamp":1784278852000},"page":"2493","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Quantum Chemical Insights into Antibiotic Structure-Activity Relationships and Mechanisms of Action: A Review"],"prefix":"10.3390","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9621-3534","authenticated-orcid":false,"given":"Seitzhan","family":"Turganbay","sequence":"first","affiliation":[{"name":"JSC Scientific Center for Anti-Infectious Drugs, Almaty 050060, Kazakhstan"},{"name":"Faculty of Natural Sciences, Kazakh National Women\u2019s Teacher Training University, Almaty 050000, Kazakhstan"},{"name":"\u201cOne Belt, One Road\u201d Petroleum Engineering, Kazakh British Technical University, Almaty 050000, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Ilin","sequence":"additional","affiliation":[{"name":"JSC Scientific Center for Anti-Infectious Drugs, Almaty 050060, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3677-8685","authenticated-orcid":false,"given":"Aitugan","family":"Sabitov","sequence":"additional","affiliation":[{"name":"Faculty of Natural Sciences, Kazakh National Women\u2019s Teacher Training University, Almaty 050000, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingcheng","family":"Hao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Colloid and Interface Chemistry, Ministry of Education, Shandong University, Jinan 250100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7791-3145","authenticated-orcid":false,"given":"Anar","family":"Seisembekova","sequence":"additional","affiliation":[{"name":"JSC Scientific Center for Anti-Infectious Drugs, Almaty 050060, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amir","family":"Azembaev","sequence":"additional","affiliation":[{"name":"JSC Scientific Center for Anti-Infectious Drugs, Almaty 050060, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-0471-0587","authenticated-orcid":false,"given":"Daniil","family":"Shepilov","sequence":"additional","affiliation":[{"name":"JSC Scientific Center for Anti-Infectious Drugs, Almaty 050060, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,17]]},"reference":[{"key":"ref_1","first-page":"277","article-title":"The antibiotic resistance crisis: Part 1: Causes and threats","volume":"40","author":"Ventola","year":"2015","journal-title":"Pharm. Ther."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"105923","DOI":"10.1016\/j.micpath.2022.105923","article-title":"Emergent crisis of antibiotic resistance: A silent pandemic threat to 21st century","volume":"174","author":"Akram","year":"2023","journal-title":"Microb. Pathog."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1146\/annurev.physchem.55.091602.094410","article-title":"Ab initio quantum chemical and mixed quantum mechanics\/molecular mechanics (QM\/MM) methods for studying enzymatic catalysis","volume":"56","author":"Friesner","year":"2005","journal-title":"Annu. Rev. Phys. Chem."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Tzeliou, C.E., Mermigki, M.A., and Tzeli, D. (2022). Review on the QM\/MM methodologies and their application to metalloproteins. Molecules, 27.","DOI":"10.3390\/molecules27092660"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e27544","DOI":"10.1002\/jcc.27544","article-title":"Mechanism of ampicillin hydrolysis by New Delhi metallo-\u03b2-lactamase 1: Insight from QM\/MM MP2 calculation","volume":"46","author":"Lai","year":"2025","journal-title":"J. Comput. Chem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1007\/s10822-012-9630-6","article-title":"A Quantum Mechanics\/Molecular Mechanics Study on the Hydrolysis Mechanism of New Delhi Metallo-\u03b2-Lactamase-1","volume":"27","author":"Zhu","year":"2013","journal-title":"J. Comput. Aided Mol. Des."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2627","DOI":"10.1039\/C9SC06460E","article-title":"Metal complexes as a promising source for new antibiotics","volume":"11","author":"Frei","year":"2020","journal-title":"Chem. Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"11153","DOI":"10.3390\/molecules180911153","article-title":"Metal complexes of quinolone antibiotics and their applications: An update","volume":"18","author":"Uivarosi","year":"2013","journal-title":"Molecules"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Chai, W.C., Whittall, J.J., Song, D., Polyak, S.W., Ogunniyi, A.D., Wang, Y., Bi, F., Ma, S., Semple, S.J., and Venter, H. (2020). Antimicrobial action and reversal of resistance in MRSA by difluorobenzamide derivatives targeted at FtsZ. Antibiotics, 9.","DOI":"10.3390\/antibiotics9120873"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Rodr\u00edguez, I., Fern\u00e1ndez-Vega, L., Maser-Figueroa, A.N., Sang, B., Gonz\u00e1lez-Pag\u00e1n, P., and Tinoco, A.D. (2022). Exploring titanium (IV) complexes as potential antimicrobial compounds. Antibiotics, 11.","DOI":"10.3390\/antibiotics11020158"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Griffiths, D.J., and Schroeter, D.F. (2018). Introduction to Quantum Mechanics, Cambridge University Press. [3rd ed.].","DOI":"10.1017\/9781316995433"},{"key":"ref_12","unstructured":"Rodrigues, S.B.F., de Ara\u00fajo, R.S.A., de Mendon\u00e7a, T.R.D., Mendon\u00e7a-J\u00fanior, F.J.B., Zhan, P., and da Silva-J\u00fanior, E.F. (2023). Quantum Chemistry in Drug Design: Density Function Theory (DFT) and Other Quantum Mechanics (QM)-Related Approaches. Applied Computer-Aided Drug Design: Models and Methods, Bentham Science Publishers."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"6598","DOI":"10.1021\/acs.jcim.3c01245","article-title":"Conformer Generation for Structure-Based Drug Design: How Many and How Good?","volume":"63","author":"McNutt","year":"2023","journal-title":"J. Chem. Inf. Model."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1038\/s41570-023-00563-1","article-title":"Molecular Chameleons in Drug Discovery","volume":"8","author":"Poongavanam","year":"2024","journal-title":"Nat. Rev. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"103374","DOI":"10.1016\/j.drudis.2022.103374","article-title":"Benefits of Hybrid QM\/MM over Traditional Classical Mechanics in Pharmaceutical Systems","volume":"28","author":"Kar","year":"2023","journal-title":"Drug Discov. Today"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.sbi.2021.07.004","article-title":"Harder, Better, Faster, Stronger: Large-Scale QM and QM\/MM for Predictive Modeling in Enzymes and Proteins","volume":"72","author":"Vennelakanti","year":"2022","journal-title":"Curr. Opin. Struct. Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"37","DOI":"10.56782\/pps.412","article-title":"In Silico Prediction of Some Indole Derivatives against VirB8 from Brucella suis and Cyanobacterial Membrane-Bound Manganese Superoxide Dismutase","volume":"23","author":"Surana","year":"2025","journal-title":"Prospect. Pharm. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"50","DOI":"10.56782\/pps.341","article-title":"Curbing Anti-Microbial Resistance of Synthetic Medicinal Agents Using Herbal Drug Alternatives: Current Trends and Future Insights","volume":"23","author":"Bushra","year":"2025","journal-title":"Prospect. Pharm. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"12598","DOI":"10.1021\/acsomega.1c00592","article-title":"Theoretical Study on the Mechanism of the Acylate Reaction of \u03b2-Lactamase","volume":"6","author":"Wei","year":"2021","journal-title":"ACS Omega"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"14679","DOI":"10.1021\/ja405319n","article-title":"Mechanism of Acyl-Enzyme Complex Formation from the Henry-Michaelis Complex of Class C \u03b2-Lactamases with \u03b2-Lactam Antibiotics","volume":"135","author":"Tripathi","year":"2013","journal-title":"J. Am. Chem. Soc."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2681","DOI":"10.1021\/acs.jpcb.5b11623","article-title":"Deacylation Mechanism and Kinetics of Acyl-Enzyme Complex of Class C \u03b2-Lactamase and Cephalothin","volume":"120","author":"Tripathi","year":"2016","journal-title":"J. Phys. Chem. B"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4299","DOI":"10.1021\/acs.jpcb.8b01287","article-title":"Mechanism and Kinetics of Aztreonam Hydrolysis Catalyzed by Class-C \u03b2-Lactamase: A Temperature-Accelerated Sliced Sampling Study","volume":"122","author":"Awasthi","year":"2018","journal-title":"J. Phys. Chem. B"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"13111","DOI":"10.1039\/C6CP08769H","article-title":"Hydrolysis of Cephalexin and Meropenem by New Delhi Metallo-\u03b2-Lactamase: The Substrate Protonation Mechanism Is Drug Dependent","volume":"19","author":"Das","year":"2017","journal-title":"Phys. Chem. Chem. Phys."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3121","DOI":"10.1021\/acs.jctc.0c00153","article-title":"Both Configuration and QM Region Size Matter: Zinc Stability in QM\/MM Models of DNA Methyltransferase","volume":"16","author":"Mehmood","year":"2020","journal-title":"J. Chem. Theory Comput."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"5191","DOI":"10.1021\/acs.biochem.6b00461","article-title":"Insight into the Mechanism of Hydrolysis of Meropenem by OXA-23 Serine-\u03b2-Lactamase Gained by Quantum Mechanics\/Molecular Mechanics Calculations","volume":"55","author":"Sgrignani","year":"2016","journal-title":"Biochemistry"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1378","DOI":"10.1021\/acs.jpcb.7b10188","article-title":"Modeling the Transient Kinetics of the L1 Metallo-\u03b2-Lactamase","volume":"122","author":"Khrenova","year":"2018","journal-title":"J. Phys. Chem. B"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"5658","DOI":"10.1021\/acs.jcim.1c01109","article-title":"Multiscale Workflow for Modeling Ligand Complexes of Zinc Metalloproteins","volume":"61","author":"Yang","year":"2021","journal-title":"J. Chem. Inf. Model."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"5419","DOI":"10.1021\/acs.jctc.8b00670","article-title":"QM\/MM Calculations on Protein\u2013RNA Complexes: Understanding Limitations of Classical MD Simulations and Search for Reliable Cost-Effective QM Methods","volume":"14","author":"Kruse","year":"2018","journal-title":"J. Chem. Theory Comput."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"102417","DOI":"10.1016\/j.sbi.2022.102417","article-title":"Computer-Aided Drug Design: Quantum Mechanical Methods for Biological Problems","volume":"75","author":"Manathunga","year":"2022","journal-title":"Curr. Opin. Struct. Biol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Niazi, S.K. (2025). Quantum Mechanics in Drug Discovery: A Comprehensive Review of Methods, Applications, and Future Directions. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26136325"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1016\/S0140-6736(21)02724-0","article-title":"Global Burden of Bacterial Antimicrobial Resistance in 2019: A Systematic Analysis","volume":"399","author":"Murray","year":"2022","journal-title":"Lancet"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1038\/nrmicro3380","article-title":"Molecular Mechanisms of Antibiotic Resistance","volume":"13","author":"Blair","year":"2015","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1432","DOI":"10.1038\/s41564-019-0503-9","article-title":"Defining and Combating Antibiotic Resistance from One Health and Global Health Perspectives","volume":"4","author":"Coque","year":"2019","journal-title":"Nat. Microbiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1021\/acscatal.1c04786","article-title":"QM\/MM Study of a VIM-1 Metallo-\u03b2-Lactamase Enzyme: The Catalytic Reaction Mechanism","volume":"12","author":"Medina","year":"2022","journal-title":"ACS Catal."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1521","DOI":"10.1021\/acsinfecdis.2c00152","article-title":"QM\/MM Simulations Reveal the Determinants of Carbapenemase Activity in Class A \u03b2-Lactamases","volume":"8","author":"Chudyk","year":"2022","journal-title":"ACS Infect. Dis."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Huang, Y.-S., and Zhou, H. (2025). Breakthrough Advances in Beta-Lactamase Inhibitors: New Synthesized Compounds and Mechanisms of Action Against Drug-Resistant Bacteria. Pharmaceuticals, 18.","DOI":"10.20944\/preprints202501.0030.v1"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1021\/acsinfecdis.2c00395","article-title":"Difference in the Inhibitory Effect of Thiol Compounds and Demetallation Rates from the Zn(II) Active Site of Metallo-\u03b2-Lactamases (IMP-1 and IMP-6) Associated with a Single Amino Acid Substitution","volume":"9","author":"Yamaguchi","year":"2023","journal-title":"ACS Infect. Dis."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"5667","DOI":"10.1128\/AAC.01276-12","article-title":"Mutagenesis of Zinc Ligand Residue Cys221 Reveals Plasticity in the IMP-1 Metallo-\u03b2-Lactamase Active Site","volume":"56","author":"Horton","year":"2012","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1039\/C4MT00066H","article-title":"A Variety of Roles for Versatile Zinc in Metallo-\u03b2-Lactamases","volume":"6","author":"Karsisiotis","year":"2014","journal-title":"Metallomics"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1016\/j.molstruc.2018.08.082","article-title":"Synthesis, Spectroscopic Studies, DFT Calculations, Cytotoxicity and Antimicrobial Activity of Some Metal Complexes with Ofloxacin and 2,2\u2032-Bipyridine","volume":"1176","author":"Sadeek","year":"2019","journal-title":"J. Mol. Struct."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Shepilov, D., Askarova, D., Seisembekova, A., Turganbay, S., Jumagaziyeva, A., Bukeyeva, T., Yuldasheva, G., Temir, N., Ivanova, L.N., and Zubenko, N. (2026). Iodine-Based Coordination Compounds: A Strategy Toward Antibiotic Potentiation. Int. J. Mol. Sci., 27.","DOI":"10.20944\/preprints202604.1049.v1"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"120264","DOI":"10.1016\/j.ica.2021.120264","article-title":"Crystal Structure, Spectroscopic, DFT Calculations and Antimicrobial Study of the Cu(II) Complex Bearing Second-Generation Quinolone Ofloxacin and 2,2\u2032-Bipyridine","volume":"519","author":"Baleye","year":"2021","journal-title":"Inorganica Chim. Acta"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"111087","DOI":"10.1016\/j.inoche.2023.111087","article-title":"Synthesis, Characterization, DFT, Biological and Molecular Docking of Mixed Ligand Complexes of Ni(II), Co(II), and Cu(II) Based on Ciprofloxacin and 2-(1H-Benzimidazol-2-yl)Phenol","volume":"155","author":"Khalaf","year":"2023","journal-title":"Inorg. Chem. Commun."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"10252","DOI":"10.1063\/1.1361246","article-title":"Introduction of a n-electron valence state perturbation theory based on a CASSCF reference wave function","volume":"114","author":"Angeli","year":"2001","journal-title":"J. Chem. Phys."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"129832","DOI":"10.1016\/j.molstruc.2020.129832","article-title":"Mixed-Ligand Complexes of Ampicillin Derived Schiff Base Ligand and Nicotinamide: Synthesis, Physico-Chemical Studies, DFT Calculation, Antibacterial Study and Molecular Docking Analysis","volume":"1229","author":"Mohapatra","year":"2021","journal-title":"J. Mol. Struct."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"150509","DOI":"10.1016\/j.scitotenv.2021.150509","article-title":"Quantum Chemical Prediction of Effects of Temperature on Hydrolysis Rate of Penicillin under Weakly Acidic Condition","volume":"806","author":"Zhang","year":"2022","journal-title":"Sci. Total Environ."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Shepilov, D., Turganbay, S., Jumagaziyeva, A., Bukeyeva, T., Askarova, D., Bolatova, D., Doszhanov, Y., Zhumazhanov, A., Kerimkulova, A., and Saurykova, K. (2025). The Iodine\u2013Dextrin\u2013Lithium Complex: Morphology, Antibacterial Activity, and Cytotoxicity. Molecules, 30.","DOI":"10.20944\/preprints202511.1426.v1"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Ibragimova, N., Aitynova, A., Turganbay, S., Lyu, M., Ilin, A., Vassilyeva, K., Issayeva, D., Gapurkhaeva, T., Krasnoshtanov, A., and Ponomareva, G. (2025). A Novel Iodine\u2013Dextrin Complex Exhibits No Acute or Subacute Toxicity and Enhances Azithromycin Efficacy in an LPS-Induced Sepsis Model. Pharmaceutics, 17.","DOI":"10.3390\/pharmaceutics17081040"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Severoglu, Y.B., Yuksel, B., Sucu, C., Aral, N., Uversky, V.N., and Coskuner-Weber, O. (2025). Implicit Solvent Models and Their Applications in Biophysics. Biomolecules, 15.","DOI":"10.20944\/preprints202507.2627.v1"},{"key":"ref_50","unstructured":"\u00d6zt\u00fcrk, F., and Aycan, T. (2023). DFT, Hirshfeld Surface Analysis and Molecular Docking, Drug-Likeness and ADME of Zn(II)-Sulfamethoxazole Complex with Diethylenetriamine Ligands, SRA Academic Publishing."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"3799","DOI":"10.1039\/D5MD00221D","article-title":"Design, synthesis and computational approach of vanillyl-imidazolidinyl-sulfamethoxazole derivatives as potent antimicrobial candidates tackling microbial resistance","volume":"16","author":"Panda","year":"2025","journal-title":"RSC Med. Chem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"6615","DOI":"10.1039\/b810189b","article-title":"Long-range corrected hybrid density functionals with damped atom-atom dispersion corrections","volume":"10","author":"Chai","year":"2008","journal-title":"Phys. Chem. Chem. Phys."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Zhang, R., Wang, Y., Liu, H., and Chen, X. (2025). Recent Applications of Schiff Bases in Biomedical Sciences. Schiff Bases and Their Metal Complexes: Advances in Biomedical Applications, IntechOpen.","DOI":"10.5772\/intechopen.1011068"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"9598","DOI":"10.1039\/D1NJ00293G","article-title":"Synthesis and Theoretical Calculations of Metal-Antibiotic Chelation with Thiamphenicol: In Vitro DNA and HSA Binding, Molecular Docking, and Cytotoxicity Studies","volume":"45","author":"Sharfalddin","year":"2021","journal-title":"New J. Chem."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"117275","DOI":"10.1016\/j.envres.2023.117275","article-title":"Imipenem-Metal Complexes: Computational Analysis and Toxicity Studies with Wastewater Model Microorganisms","volume":"239","author":"Khurana","year":"2023","journal-title":"Environ. Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1038\/nrmicro3155","article-title":"Ribosome-Targeting Antibiotics and Mechanisms of Bacterial Resistance","volume":"12","author":"Wilson","year":"2014","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1438","DOI":"10.1021\/ja016830+","article-title":"Binding of Aminoglycoside Antibiotics to the Small Ribosomal Subunit: A Continuum Electrostatics Investigation","volume":"124","author":"Ma","year":"2002","journal-title":"J. Am. Chem. Soc."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"4872","DOI":"10.1093\/nar\/gky221","article-title":"Influence of Na+ and Mg2+ ions on RNA structures studied with molecular dynamics simulations","volume":"46","author":"Fischer","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"108817","DOI":"10.1016\/j.jmgm.2024.108817","article-title":"A Computational Workflow to Determine Drug Candidates Alternative to Aminoglycosides Targeting the Decoding Center of Escherichia coli Ribosome","volume":"131","author":"Yuce","year":"2024","journal-title":"J. Mol. Graph. Model."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"6421","DOI":"10.1021\/acs.jpcb.9b04468","article-title":"Ribosomal RNA\u2013Aminoglycoside Hygromycin B Interaction Energy Calculation within a Density Functional Theory Framework","volume":"123","author":"Bezerra","year":"2019","journal-title":"J. Phys. Chem. B"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Turganbay, S., Kenesheva, S., Jumagaziyeva, A., Ilin, A., Askarova, D., Azembayev, A., and Kurmanaliyeva, A. (2024). Synthesis, Physicochemical Properties and Antimicrobial Activity of a Diaminopropionic Acid Hydrogen Tri-Iodide Coordination Compound. BMC Res. Notes, 17.","DOI":"10.1186\/s13104-024-07052-8"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2727","DOI":"10.1007\/s00894-011-1272-4","article-title":"Quantum Mechanical Studies of Lincosamides","volume":"18","author":"Trylska","year":"2012","journal-title":"J. Mol. Model."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2849","DOI":"10.1128\/AAC.04895-14","article-title":"Structural Characterization of an Alternative Mode of Tigecycline Binding to the Bacterial Ribosome","volume":"59","author":"Schedlbauer","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Ojo, O.A., Ojo, A.B., Okolie, C., Nwakama, M.C., Iyobhebhe, M., Evbuomwan, I.O., Nwonuma, C.O., Maimako, R.F., Adegboyega, A.E., and Taiwo, O.A. (2021). Deciphering the interactions of bioactive compounds in selected traditional medicinal plants against Alzheimer\u2019s diseases via pharmacophore modeling, Auto-QSAR, and molecular docking approaches. Molecules, 26.","DOI":"10.3390\/molecules26071996"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1582","DOI":"10.1080\/07391102.2018.1462731","article-title":"Multiple e-Pharmacophore Modeling to Identify a Single Molecule That Could Target Both Streptomycin and Paromomycin Binding Sites for 30S Ribosomal Subunit Inhibition","volume":"37","author":"CP","year":"2019","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"415","DOI":"10.3762\/bjoc.12.45","article-title":"Effective In Silico Prediction of New Oxazolidinone Antibiotics: Force Field Simulations of the Antibiotic-Ribosome Complex Supervised by Experiment and Electronic Structure Methods","volume":"12","author":"Grunenberg","year":"2016","journal-title":"Beilstein J. Org. Chem."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.2217\/pgs.10.18","article-title":"Pharmacogenomic Strategies against Microbial Resistance: From Bright to Bleak to Innovative","volume":"11","author":"Dandekar","year":"2010","journal-title":"Pharmacogenomics"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"e23629","DOI":"10.1002\/chir.23629","article-title":"Theoretical Study of the Interaction between the Antibiotic Linezolid and the Active Site of the 50S Ribosomal Subunit of the Bacterium Haloarcula marismortui","volume":"36","author":"Grandini","year":"2024","journal-title":"Chirality"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1007\/s00284-001-0023-7","article-title":"Linezolid Is a Specific Inhibitor of 50S Ribosomal Subunit Formation in Staphylococcus aureus Cells","volume":"44","author":"Champney","year":"2002","journal-title":"Curr. Microbiol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"17158","DOI":"10.1073\/pnas.1008685107","article-title":"Revisiting the Structures of Several Antibiotics Bound to the Bacterial Ribosome","volume":"107","author":"Bulkley","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"17152","DOI":"10.1073\/pnas.1007988107","article-title":"Structures of the Escherichia coli Ribosome with Antibiotics Bound Near the Peptidyl Transferase Center Explain Spectra of Drug Action","volume":"107","author":"Dunkle","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"5982","DOI":"10.1093\/nar\/gkq411","article-title":"Structural Signatures of Antibiotic Binding Sites on the Ribosome","volume":"38","author":"Mankin","year":"2010","journal-title":"Nucleic Acids Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1126\/science.adk8013","article-title":"An Antibiotic Preorganized for Ribosomal Binding Overcomes Antimicrobial Resistance","volume":"383","author":"Wu","year":"2024","journal-title":"Science"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"113696","DOI":"10.1016\/j.ejmech.2021.113696","article-title":"Discovery of Metal-Based Complexes as Promising Antimicrobial Agents","volume":"224","author":"Hao","year":"2021","journal-title":"Eur. J. Med. Chem."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1038\/nrd4706","article-title":"A Community-Based Approach to New Antibiotic Discovery","volume":"14","author":"Cooper","year":"2015","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"6679","DOI":"10.1021\/jm0505112","article-title":"Antibiotic Binding to Monozinc CphA \u03b2-Lactamase from Aeromonas hydrophila: Quantum Mechanical\/Molecular Mechanical and Density Functional Theory Studies","volume":"48","author":"Xu","year":"2005","journal-title":"J. Med. Chem."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"5630","DOI":"10.1021\/jp068746s","article-title":"Antibiotic Binding to Dizinc \u03b2-Lactamase L1 from Stenotrophomonas maltophilia: SCC-DFTB\/CHARMM and DFT Studies","volume":"111","author":"Xu","year":"2007","journal-title":"J. Phys. Chem. A"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"10814","DOI":"10.1021\/ja072532m","article-title":"Antibiotic Deactivation by a Dizinc \u03b2-Lactamase: Mechanistic Insights from QM\/MM and DFT Studies","volume":"129","author":"Xu","year":"2007","journal-title":"J. Am. Chem. Soc."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"4454","DOI":"10.1021\/ja044210d","article-title":"Mechanisms of Antibiotic Resistance: QM\/MM Modeling of the Acylation Reaction of a Class A \u03b2-Lactamase with Benzylpenicillin","volume":"127","author":"Hermann","year":"2005","journal-title":"J. Am. Chem. Soc."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"4232","DOI":"10.1021\/ja042607b","article-title":"Hybrid QM\/MM and DFT Investigations of the Catalytic Mechanism and Inhibition of the Dinuclear Zinc Metallo-\u03b2-Lactamase CcrA from Bacteroides fragilis","volume":"127","author":"Park","year":"2005","journal-title":"J. Am. Chem. Soc."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"8664","DOI":"10.1039\/C9RA10649A","article-title":"Revealing Electronic Features Governing Hydrolysis of Cephalosporins in the Active Site of the L1 Metallo-\u03b2-Lactamase","volume":"10","author":"Levina","year":"2020","journal-title":"RSC Adv."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"2521","DOI":"10.1021\/cs5002898","article-title":"Catalytic Cycle of Penicillin Acylase from Escherichia coli: QM\/MM Modeling of Chemical Transformations in the Enzyme Active Site upon Penicillin G Hydrolysis","volume":"4","author":"Grigorenko","year":"2014","journal-title":"ACS Catal."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"11581","DOI":"10.1021\/bi050797c","article-title":"Enzyme-Substrate Interactions with an Antibiotic Resistance Enzyme: Aminoglycoside Nucleotidyltransferase(2\u2033)-Ia Characterized by Kinetic and Thermodynamic Methods","volume":"44","author":"Wright","year":"2005","journal-title":"Biochemistry"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"60874","DOI":"10.1021\/acsomega.5c09502","article-title":"Dynamical fragment molecular orbital interaction analysis of SARS-CoV-2 RNA-dependent RNA polymerase and remdesivir","volume":"10","author":"Miyakawa","year":"2025","journal-title":"ACS Omega"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1164","DOI":"10.1038\/s41597-024-03999-2","article-title":"Quantum Chemical Calculation Dataset for Representative Protein Folds by the Fragment Molecular Orbital Method","volume":"11","author":"Takaya","year":"2024","journal-title":"Sci. Data"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1063\/1.476673","article-title":"6-31G* Basis Set for Atoms K through Zn","volume":"109","author":"Rassolov","year":"1998","journal-title":"J. Chem. Phys."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"9525","DOI":"10.1021\/jp100579y","article-title":"Absolute Binding Free Energy Calculations of Sparsomycin Analogs to the Bacterial Ribosome","volume":"114","author":"Ge","year":"2010","journal-title":"J. Phys. Chem. B"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/S0021-9673(01)01337-1","article-title":"Non-Derivatization Approach to High-Performance Liquid Chromatography-Fluorescence Detection for Aminoglycoside Antibiotics Based on a Ligand Displacement Reaction","volume":"939","author":"Yang","year":"2001","journal-title":"J. Chromatogr. A"},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Am\u00e1bile-Cuevas, C.F., and Lund-Zaina, S. (2024). Non-Canonical Aspects of Antibiotics and Antibiotic Resistance. Antibiotics, 13.","DOI":"10.3390\/antibiotics13060565"},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Kircheva, N., Petkova, V., Angelova, S., and Dudev, T. (2026). DFT evaluation of metal ion selectivity in protein phosphatase PPM1A: The effect of native metal type and multiplicity on the competition with other biogenic contenders for the active site. Biomolecules, 16.","DOI":"10.3390\/biom16060860"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"13151","DOI":"10.1038\/s41598-026-41979-1","article-title":"Synthesis, spectroscopic investigation, theoretical insights via DFT and biological assessment of some isatin-based metal complexes","volume":"16","author":"Tolan","year":"2026","journal-title":"Sci. Rep."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/31\/14\/2493\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T09:01:12Z","timestamp":1784278872000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/31\/14\/2493"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,17]]},"references-count":91,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["molecules31142493"],"URL":"https:\/\/doi.org\/10.3390\/molecules31142493","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,17]]}}}